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The Xenopus community has embraced recent advances in sequencing technology, resulting in the accumulation of numerous RNA-Seq and ChIP-Seq datasets. However, easily accessing and comparing datasets generated by multiple laboratories is challenging. Thus, we have created a central space to view, search and analyze data, providing essential information on gene expression changes and regulatory elements present in the genome. XenMine (www.xenmine.org) is a user-friendly website containing published genomic datasets from both Xenopus tropicalis and Xenopus laevis. We have established an analysis pipeline where all published datasets are uniformly processed with the latest genome releases. Information from these datasets can be extracted and compared using an array of pre-built or custom templates. With these search tools, users can easily extract sequences for all putative regulatory domains surrounding a gene of interest, identify the expression values of a gene of interest over developmental time, and analyze lists of genes for gene ontology terms and publications. Additionally, XenMine hosts an in-house genome browser that allows users to visualize all available ChIP-Seq data, extract specifically marked sequences, and aid in identifying important regulatory elements within the genome. Altogether, XenMine is an excellent tool for visualizing, accessing and querying analyzed datasets rapidly and efficiently., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In the vertebrate blastula and gastrula the Nodal pathway is essential for formation of the primary germ layers and the organizer. Nodal autoregulatory feedback potentiates signaling activity, but mechanisms limiting embryonic Nodal ligand transcription are poorly understood. Here we describe a transcriptional switch mechanism mediated by FoxH1, the principle effector of Nodal autoregulation. FoxH1 contains a conserved engrailed homology (EH1) motif that mediates direct binding of groucho-related gene 4 (Grg4), a Groucho family corepressor. Nodal-dependent gene expression is suppressed by FoxH1, but enhanced by a FoxH1 EH1 mutant, indicating that the EH1 motif is necessary for repression. Grg4 blocks Nodal-induced mesodermal gene expression and Nodal autoregulation, suggesting that Grg4 limits Nodal pathway activity. Conversely, blocking Grg4 function in the ectoderm results in ectopic expression of Nodal target genes. FoxH1 and Grg4 occupy the Xnr1 enhancer, and Grg4 occupancy is dependent on the FoxH1 EH1 motif. Grg4 occupancy at the Xnr1 enhancer significantly decreases with Nodal activation or Smad2 overexpression, while FoxH1 occupancy is unaffected. These results suggest that Nodal-activated Smad2 physically displaces Grg4 from FoxH1, an essential feature of the transcriptional switch mechanism. In support of this model, when FoxH1 is unable to bind Smad2, Grg4 occupancy is maintained at the Xnr1 enhancer, even in the presence of Nodal signaling. Our findings reveal that FoxH1 mediates both activation and repression of Nodal gene expression. We propose that this transcriptional switch is essential to delimit Nodal pathway activity in vertebrate germ layer formation., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Signaling inputs from multiple pathways are essential for the establishment of distinct cell and tissue types in the embryo. Therefore, multiple signals must be integrated to activate gene expression and confer cell fate, but little is known about how this occurs at the level of target gene promoters. During early embryogenesis, Wnt and Nodal signals are required for formation of the Spemann organizer, which is essential for germ layer patterning and axis formation. Signaling by both Wnt and Nodal pathways is required for the expression of multiple organizer genes, suggesting that integration of these signals is required for organizer formation. Here, we demonstrate transcriptional cooperation between the Wnt and Nodal pathways in the activation of the organizer genes Goosecoid (Gsc), Cerberus (Cer), and Chordin (Chd). Combined Wnt and Nodal signaling synergistically activates transcription of these organizer genes. Effectors of both pathways occupy the Gsc, Cer and Chd promoters and effector occupancy is enhanced with active Wnt and Nodal signaling. This suggests that, at organizer gene promoters, a stable transcriptional complex containing effectors of both pathways forms in response to combined Wnt and Nodal signaling. Consistent with this idea, the histone acetyltransferase p300 is recruited to organizer promoters in a Wnt and Nodal effector-dependent manner. Taken together, these results offer a mechanism for spatial and temporal restriction of organizer gene transcription by the integration of two major signaling pathways, thus establishing the Spemann organizer domain., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The Spemann organizer is an essential signaling center in Xenopus germ layer patterning and axis formation. Organizer formation occurs in dorsal blastomeres receiving both maternal Wnt and zygotic Nodal signals. In response to stabilized βcatenin, dorsal blastomeres express the closely related transcriptional activators, Siamois (Sia) and Twin (Twn), members of the paired homeobox family. Sia and Twn induce organizer formation and expression of organizer-specific genes, including Goosecoid (Gsc). In spite of the similarity of Sia and Twn sequence and expression pattern, it is unclear whether these factors function equivalently in promoter binding and subsequent transcriptional activation, or if Sia and Twn are required for all aspects of organizer function. Here we report that Sia and Twn activate Gsc transcription by directly binding to a conserved P3 site within the Wnt-responsive proximal element of the Gsc promoter. Sia and Twn form homodimers and heterodimers by direct homeodomain interaction and dimer forms are indistinguishable in both DNA-binding and activation functions. Sequential chromatin immunoprecipitation reveals that the endogenous Gsc promoter can be occupied by either Sia or Twn homodimers or Sia-Twn heterodimers. Knockdown of Sia and Twn together, but not individually, results in a failure of organizer gene expression and a disruption of axis formation, consistent with a redundant role for Sia and Twn in organizer formation. Furthermore, simultaneous knockdown of Sia and Twn blocks axis induction in response to ectopic Wnt signaling, demonstrating an essential role for Sia and Twn in mediating the transcriptional response to the maternal Wnt pathway. The results demonstrate the functional redundancy of Sia and Twn and their essential role in direct transcriptional responses necessary for Spemann organizer formation., (Copyright © 2011 Elsevier Inc. All rights reserved.)

A post-traumatic cyst is a rare complication of significant soft tissue trauma. It occurs at the junction between the subcutaneous fat and underlying fascia, when a large, subcutaneous haematoma fails to resolve, developing into a chronic, fluid-filled cyst, lined with fibrous tissue. This results in a swelling that persists for years, gradually increasing in size, often without causing significant discomfort to the patient. Clinically and radiologically these swellings may be mistaken for neoplastic lesions. They can be difficult to treat, are refractory to conservative management and have a high rate of recurrence following surgical excision. Careful monitoring and early treatment of persistent postoperative seroma is advocated.

We present a case of multiple primary malignant melanomata occurring over a six year period in a 63-year-old Caucasian man with neurofibromatosis type 1. There is doubt regarding a definite association between these two diseases despite a number of case reports and clear, potential pathological mechanisms. This case not only strengthens support for an association but also highlights the great difficulties that arise in the management of cutaneous melanomata in patients with neurofibromatosis.

Juvenile xanthogranuloma is a relatively rare cutaneous lesion. In order to make an early diagnosis and be alert to the possibility of visceral complications and associated medical conditions, plastic surgeons should be aware of the entity. The classic presentation is that of successive eruptions in the head, neck and upper trunk of initially red papules or nodules which later become yellow and finally brown flattened plaques or macules. This report is of an unusual variant with atypical histology including frequent mitoses and a lack of Touton giant cells., (Copyright 1999 The British Association of Plastic Surgeons.)

We have identified a new recurrent reciprocal translocation between chromosome 3 and 12 with breakpoints at bands 3q26 and 12p13, t(3;12)(q26;p13) in the malignant cells from five patients with acute transformation of myelodysplastic syndrome or blast crisis of chronic myelogenous leukemia. t(3;12)(q26;p13) appears as a rare but nonrandom event present in various myeloid leukemia subtypes, which is frequently associated with dysplasia of megakaryocytes, multilineage involvement, short duration of any blastic phase, and a very poor prognosis. Here, we report the molecular cytogenetic analysis of the t(3;12). Fluorescence in situ hybridization results indicate that the 3q26 breakpoints are quite heterogeneous and occur 5' of MDS1, 3' of EVI1, or between MDS1 and EVI1. Our results are very similar to those observed in other 3q26 rearrangements in which breakpoints were shown to occur over considerable distances 5' and 3' of EVI1. Fluorescence in situ hybridization investigations proved that, in three myelodysplastic syndrome cases with t(3;12)(q26;p13), the 12p 13 breakpoint occurred within the TEL gene.

This paper reports our experience of the use of polythene sheet as a temporary dressing for excised wounds. A prospective randomised double-blind trial was conducted to see whether or not polythene dressing was less painful to remove than our traditional dressing of Jelonet. Polythene was found to be less painful (p less than 0.01). Other advantages of the use of polythene are presented.

The effective coding of data to produce a medical audit relies on agreement between the coders. This study was designed to assess whether coders can agree on codes for diagnosis and operations in a plastic surgery unit. Information from 50 patients was presented to a panel of six coders who were required to code the data using the International Classification of Diseases (ICD-9) and the Office of Population Census Studies (OPCS-4) systems. The results show that agreement between all the panellists occurred in only 32 out of 50 patients for one diagnostic code and 30 out of 50 for one operation code. When a patient had more than one diagnosis or operation, agreement was very much worse. Expert coders produced better results than the medical coders. The results are discussed with reference to other coding systems.

Colonies of cells with distinctive dendritic appearance were observed in methylcellulose cultures of human bone marrow and peripheral blood mononuclear cells (PBMC). Such cells appeared alone in colonies of less than 50 cells, together with macrophages in mixed colonies and also within clusters of T lymphocytes at high culture cell numbers. The morphologic resemblance to lymphoid dendritic cells was confirmed by electron microscopy and the cells were distinguished from macrophages by immunoenzymatic and immunogold labeling with monoclonal antibodies (MoAbs). Like macrophages they were HLA-DR+ and CD4+. However, they lacked nonspecific esterase and the macrophage cytoplasmic marker Y1/82A. Most strikingly, cells were strongly HLA-DQ+ and expressed CD1a (T6), which is characteristic of skin Langerhans cells. Their functional similarity to lymphoid dendritic cells was demonstrated by their ability to stimulate allogeneic mixed leukocyte reactions. Dendritic cell colony numbers were estimated in both bone marrow and peripheral blood of controls and in leukemia and lymphoma patients before and after chemotherapy. Colony numbers were low in control blood and in patients before treatment (less than 1.0 to 3.7/10(5) cells). However, during hematopoietic recovery the mean value increased to 37.5/10(5) cells and this increase correlated closely with the observed increase in circulating colony forming unit-granulocyte macrophage (CFU-GM) in individual patients. Autoradiographic studies demonstrated mitotic activity within CD1a+ colonies and a linear relationship between cultured cells and both pure and mixed colonies was consistent with their derivation from a single precursor. These data indicate that a novel hematopoietic progenitor of dendritic/Langerhans cells (DL-CFU) may now be identified in a clonal assay system and suggest a probable common progenitor for these cells and macrophages.

A single layer of surgical gauze applied with adhesive provides a simple and inexpensive dressing for use following hypospadias repair. It splints the penis to the abdomen, supports the wound and secures the catheter while permitting observation and wound care.

A technique for nasal lengthening is described in 3 cases using nasolabial flaps for lining and an island forehead flap for skin reconstruction. It is basically a 2-stage procedure with short hospitalisation.

Secondary alveolar bone grafting in cleft palate patients has been popularised by the Oslo group. Harvesting of the bone graft has been carried out by techniques developed initially for cranio-facial surgery. This paper describes a more refined technique applicable to the requirements of alveolar bone grafting. The Craig bone biopsy set is used to trephine cores of autogenous particulate marrow and cancellous bone from the iliac bone. The method was tested in a cadaver and then applied in 10 clinical cases. The aesthetic and functional results of this technique proved to be superior to the conventional approach.

A new free flap is described based on the deltoid vessels of the acromiothoracic axis. The flap is comprised of the clavicular head of pectoralis major muscle with overlying skin. It is also possible to harvest vascularised clavicular bone with the flap. The vascular anatomy is reviewed and the technique of raising the flap described. Its clinical application is illustrated with five cases. Four of these were intra-oral reconstructions and the fifth a composite osteo-musculocutaneous flap to a lower limb following trauma.

A one-stage flap repair is described for complicated dorsal injuries of the hand involving loss of skin and tendon based on the principle of the "Chinese" radial artery forearm flap in which vascularised tendons are transferred to reconstruct the missing extensor tendons.

The myeloproliferative disorders, including polycythaemia rubra vera, arise as a result of a single-cell mutation. A characteristic of the abnormal haemopoietic clone is that it can form erythroid colonies in vitro in the absence of added erythropoietin. Such endogenous erythroid clones were consistently found in two of seven patients with peripheral vascular disease. These two patients had mean platelet counts of 600 X 10(9)/l and 630 X 10(9)/l. Culture of blood and bone-marrow cells from patients with raised platelet counts secondary to a variety of other disorders failed to yield such colonies. The presence of endogenous erythroid clones provides early evidence of a myeloproliferative disorder.

A retrospective questionnaire study, by post, revealed that 69% of patients, still living following first tumour recurrence, had detected the recurrence themselves prior to routine clinic appointments. Nearly 90% developed their first recurrence in the first 5 years following primary surgical treatment. Not only could the length of routine clinic follow-up after primary melanoma treatment be shortened, but with further education of the patient and involvement of the general practitioner it seems likely that patients can be trusted to detect their own recurrences and seek appropriate advice.

"Tadpole flaps" have been used in a series of 13 cleft palate patients in attempts to close anterior palatal fistulae over a 5-year period. The technique was successful in eight patients whose fistulae remained closed. The failures are discussed in detail.

The precise vascular territory and the variations of the acromio-thoracic axis were investigated in a series of 60 fresh cadavers and 50 formalin fixed specimens using dissection, ink injection and barium radiographic studies. The sternocostal portion and the clavicular head of the pectoralis major were found to have virtually independent vascular and nerve supplies. The pectoral artery supplied the former, whereas the deltoid artery nourished the latter. The dominant supply from the pectoral artery to the rib cage was found to enter around the fourth rib in the mid clavicular line. This supply is associated with a previously undescribed origin of the pectoralis major muscle in this region. The supply to the sternum was determined as indirect via the captured territory of the internal mammary system. The dominant supply to the skin from the pectoral artery arose laterally along the free lower border of the muscle as fasciocutaneous branches. The deltoid artery supplies the skin over the shoulder by numerous small branches which emerge from the intramuscular septa of the deltoid muscle. In addition a large axial artery was noted. In most cases this arose from the deltoid artery or its acromial branch and coursed laterally. It is noteworthy that the majority of skin paddles of the pectoralis major myocutaneous flap currently used in clinical practice are designed medially and inferiorly around the perimeter of the muscle and onto the rectus sheath. In these situations such flaps are not supplied directly by the pectoral artery. In fact, they are supplied indirectly by cutaneous branches belonging to the internal mammary/superior epigastric system which are captured by arterial connections with the pectoral artery. These occur predominantly in the pectoralis major muscle. Suggestions, based on these anatomical studies, are offered to improve the versatility and safety of flaps designed in this area.

The myeloproliferative disorders are the result of an underlying abnormality of the pluripotential stem cell. One feature of this abnormality is a greatly increased sensitivity of the committed erythroid progenitors (BFU-E and CFU-E) to the hormone erythropoietin. Culture in vitro of these bone marrow or peripheral blood cells results in the growth of a proportion of colonies in the absence of added erythropoietin. These endogenous erythroid colonies (EEC) are seen in the great majority of cases of polycythaemia vera, as well as in some cases of thrombocythaemia, chronic myeloid leukaemia and idiopathic myelofibrosis. The presence of EEC appears to be a marker for the stem cell mutation and may serve to distinguish the neoplastic disorders from reactive increases of red cell mass or platelet numbers. Their absence in idiopathic erythrocytosis may also distinguish this condition from early polycythaemia vera and be useful in deciding on appropriate treatment. In patients with even a modest increase in the platelet count endogenous colonies provide firm evidence for a myeloproliferative disorder. Provision of myelosuppressive treatment can avert or improve vaso-occlusive or haemorrhagic complications. The mechanism of erythropoietin hypersensitivity is unknown but it has been shown to be a feature acquired rather late in maturation and by only a proportion of the progeny of the mutated clone. Normal erythroid progenitors co-exist with these abnormal cells in polycythaemia vera and the way in which their growth in vivo is inhibited has yet to be determined.